1. The metabolic defect in patients with Type C Niemann-Pick disease has now been established as a defect in esterification of cholesterol supplied to cells via the low-density lipoprotein (LDL) receptor or by fluid phase pinocytosis. This discovery has been extended to the development of a diagnostic test for the identification of homozygotes and for the detection of heterozygous carriers of this trait. The molecular defect in this disorder appears to be a coordinate failure to down-regulate LDL receptors on the plasma membrane of cells and the up-regulation of acyl cholesterol acyl CoA transferase, the enzyme that catalyzes the intracellular esterification of cholesterol. 2. Other work has centered on the use of non-metabolizable analogues of glucocerebroside and galactocerebroside to examine the organ and tissue disposition and excretion of these lipids that accumulate in Gaucher's disease and Krabbe's disease, respectively. A significant portion of these analogues appears in the bile of experimental animals and provides a reasonable explanation for the lack of accumulation of such lipids in hepatocytes in patients with these disorders.